Ethylmalonic Encephalopathy

DUBLIN, June 15, 2023 /PRNewswire/ -- Endo International plc (OTC: ENDPQ) announced today that one of its operating companies, Par Pharmaceutical, Inc., has begun shipping dexlansoprazole 30 mg capsules, a generic version of Takeda's Dexilant®. This additional dosage strength rounds out the product family, now with both 30 mg and 60 mg delayed-release capsules. "We're proud to provide this high-quality, affordable generic medication to appropriate patients," said Scott Sims, Senior Vice President and General Manager, Injectable Solutions & Generics at Endo. "The dexlansoprazole product family strengthens our portfolio and our reputation as a reliable supplier." Dexlansoprazole is a proton pump inhibitor with a novel delivery system approved for the treatment of erosive esophagitis and heartburn associated with symptomatic non-erosive gastroesophageal reflux disease (GERD). According to IQVIA™, Dexilant® 30 mg sales were approximately $45 million for the 12 months ended April 30, 2023. Dexilant® is a registered trademark of Takeda Pharmaceuticals U.S.A., Inc. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS Dexlansoprazole delayed-release capsules are contraindicated in patients with known hypersensitivity to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis and urticaria. PPIs, including dexlansoprazole delayed-release capsules, are contraindicated with rilpivirine-containing products. WARNINGS AND PRECAUTIONS Dexlansoprazole Delayed-Release Capsules, 60 mg, contain FD&C Yellow #5 (tartrazine) which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellow #5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity. Presence of Gastric Malignancy: In adults, symptomatic response to therapy with dexlansoprazole does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy. Acute Tubulointerstitial Nephritis (TIN): TIN has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms, from symptomatic hypersensitivity reactions to non-specific symptoms of decreased renal function (eg, malaise, nausea, anorexia). Discontinue dexlansoprazole and evaluate patients with suspected acute TIN. Clostridium difficile-Associated Diarrhea: Published observational studies suggest that PPI therapy like dexlansoprazole may be associated with an increased risk of Clostridium difficile-associated diarrhea, especially in hospitalized patients. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Bone Fracture: Several published observational studies suggest that PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the conditions being treated. Severe Cutaneous Adverse Reactions: Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs. Discontinue dexlansoprazole delayed-release capsules at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. Cutaneous and Systemic Lupus Erythematosus (CLE and SLE): CLE and SLE have been reported in patients taking PPIs. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases were CLE. The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. SLE is less commonly reported than CLE in patients receiving PPIs. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported. Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving dexlansoprazole delayed-release capsules, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Cyanocobalamin (Vitamin B12) Deficiency: Daily treatment with any acid-suppressing medications over a long period of time (eg, longer than three years) may lead to malabsorption of cyanocobalamin (Vitamin B12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. Hypomagnesemia and Mineral Metabolism: Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (eg, diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically. Interactions with Investigations for Neuroendocrine Tumors: Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop dexlansoprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. Interaction with Methotrexate: Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients. Fundic Gland Polyps: PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated. Risk of Heart Valve Thickening in Pediatric Patients Less Than Two Years of Age: Dexlansoprazole is not recommended in pediatric patients less than two years of age. ADVERSE REACTIONS Adults (≥2%): diarrhea, abdominal pain, nausea, upper respiratory tract infection, vomiting, and flatulence. Patients 12 to 17 years of age (≥5%): headache, abdominal pain, diarrhea, nasopharyngitis, and oropharyngeal pain. USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause adverse effects on fetal bone growth and development. Pediatrics: Based on data with lansoprazole, dexlansoprazole is not effective in patients with symptomatic GERD 1 month to less than 1 year of age and nonclinical studies have demonstrated adverse effects in juvenile rats. INDICATIONS AND USAGE Healing of Erosive Esophagitis (EE): Dexlansoprazole delayed-release capsules are indicated in patients 12 years of age and older for healing of all grades of EE for up to eight weeks. Maintenance of Healed Erosive Esophagitis and Relief of Heartburn: Dexlansoprazole delayed-release capsules are indicated in patients 12 years of age and older to maintain healing of EE and relief of heartburn for up to six months in adults and 16 weeks in patients 12 to 17 years of age. Treatment of Symptomatic Non-Erosive Gastroesophageal Reflux Disease: Dexlansoprazole delayed-release capsules are indicated in patients 12 years of age and older for the treatment of heartburn associated with symptomatic non-erosive gastroesophageal reflux disease (GERD) for four weeks. Please click for Full Prescribing Information. About Endo Endo (OTC: ENDPQ) is a specialty pharmaceutical company committed to helping everyone we serve live their best life through the delivery of quality, life-enhancing therapies. Our decades of proven success come from passionate team members around the globe collaborating to bring treatments forward. Together, we boldly transform insights into treatments benefiting those who need them, when they need them. Learn more at or connect with us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements Certain information in this press release may be considered "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 and any applicable Canadian securities legislation including, but not limited to, the statements by Mr. Sims, any statements relating to product launch, commercialization, sales, supply or distribution, and any statements that refer to expected, estimated or anticipated future results or that do not relate solely to historical facts. Statements including words or phrases such as "believe," "expect," "anticipate," "intend," "estimate," "plan," "will," "may," "look forward," "intend," "guidance," "future," "potential" or similar expressions are forward-looking statements. All forward-looking statements in this communication reflect the Company's current views as of the date of this communication about its plans, intentions, expectations, strategies and prospects, which are based on the information currently available to it and on assumptions it has made. Actual results may differ materially and adversely from current expectations based on a number of factors, including, among other things, the outcome of the Company's contingency planning and restructuring activities; the timing, impact or results of any pending or future litigation, investigations, proceedings or claims, including opioid, tax and antitrust related matters; any actual or contingent liabilities; settlement discussions or negotiations; the Company's liquidity, financial performance, cash position and operations; the risks and uncertainties associated with chapter 11 proceedings; the time, terms and ability to confirm a sale of the Company's businesses under Section 363 of the U.S. Bankruptcy Code; the risk that the Company's chapter 11 cases may be converted to cases under chapter 7 of the Bankruptcy Code; the adequacy of the capital resources of the Company's businesses and the difficulty in forecasting the liquidity requirements of the operations of the Company's businesses; the unpredictability of the Company's financial results; the Company's ability to discharge claims in chapter 11 proceedings; negotiations with the holders of the Company's indebtedness and its trade creditors and other significant creditors; the risks and uncertainties with performing under the terms of the restructuring support agreement and any other arrangement with lenders or creditors while in chapter 11 proceedings; the performance, including the approval, introduction, and consumer and physician acceptance of new products and the continuing acceptance of currently marketed products; and the Company's ability to obtain and successfully manufacture, maintain and distribute a sufficient supply of products to meet market demand in a timely manner. The Company expressly disclaims any intent or obligation to update these forward-looking statements, except as required to do so by law. Additional information concerning risk factors, including those referenced above, can be found in press releases issued by the Company, as well as the Company's public periodic filings with the U.S. Securities and Exchange Commission and with securities regulators in Canada, including the discussion under the heading "Risk Factors" in the Company's most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q or other filings with the U.S. Securities and Exchange Commission. SOURCE Endo International plc

- New investigational data evaluating Fexuprazan in a Korean clinical trial program for healing erosive esophagitis (EE) regardless of food intake, and in a Chinese pivotal clinical trial program for the treatment of EE SEOUL, South Korea and CHICAGO, May 19, 2023 /PRNewswire/ -- Daewoong Pharmaceutical Co., Ltd. (CEO Lee Chang-jae and Jeon Sengho) announced on the 19th that they set up a booth at the Digestive Disease Week® 2023 (DDW 2023) held in Chicago, USA and revealed new clinical data through two poster sessions demonstrating the efficacy and safety of Fexuclue® (active ingredient name: Fexuprazan) on patients with gastroesophageal reflux disease (GERD). ‌DDW is the world's largest conference where over 10,000 doctors, researchers, and gastroenterology experts are gathered from all around the world and share their recent studies and clinical practices. Throughout the conference, in addition to two poster sessions, Daewoong have a physical presence located at booth #4729, where the representatives of the company presented on-site to provide medical information regarding Daewoong's Fexuprazan and were able to make active scientific and academic exchanges with gastroenterologist from all over the world based on clinical trial results. On May 7th local time, Daewoong Pharmaceutical had two poster sessions, which were an investigator initiated trial (IIT) conducted in South Korea to compare the healing rates of a mucosal breaks by Fexuprazan before and after food intake, and a pivotal phase 3 clinical trial conducted in China to assess the efficacy and safety of Fexuprazan in treating the EE. The IIT led by Sung In-Kyung, a professor of gastroenterology at Konkuk University, assessed the efficacy and safety of Fexuprazan in patients with erosive esophagitis. The study compared the outcomes of patients who took the investigational product once a day before and after food intake. The study found no significant difference in healing rates between the group that took the investigational product before and after food intake. The ability to administer Fexuprazan irrespective of food intake provides potential differentiation from most PPIs. Professor Sung In-Kyung who oversaw the clinical trial said, "In this study, Fexuprazan is the first P-CAB agent to demonstrate equal effectiveness regardless of food intake, enabling convenient administration. At two and four weeks, Fexuprazan has shown the potential to provide a faster and stronger in suppressing the production of gastric acid than PPIs. We anticipate that the investigational use of Fexuprazan will exhibit excellent efficacy in other conditions resulting from excessive gastric acid secretion." Additionally, the randomized controlled phase 3 clinical trial that was conducted in China focusing on erosive esophagitis compared the healing rates of mucosal breaks observed through upper endoscopy over an eight-week period, which served as the effectiveness evaluation index. The study revealed that the percentage of mucosal healing rate by 8 weeks in the Fexuprazan group was 97.3% (145 out of 149 people) and that in the Esomeprazole group was 97.9% (143 out of 146 people). It demonstrates that Fexuprazan is non-inferior to Esomeprazole, which serves as an active comparator drug. Furthermore, a safety evaluation was carried out to assess adverse drug reactions, and the results were similar between Fexuprazan: (19.4%) and the active comparator drug, Esomeprazole (19.6%). No unexpected serious adverse reactions were observed, indicating its safety profile. Dr. Xiao Yinglian, the presenter of the phase 3 clinical trial in China, and a professor at Sun Yat-sen University, said, "Fexuprazan has several advantages over PPIs. It starts working within just one day and shows equal effectiveness regardless of food intake. P-CAB drugs will gradually take the place of PPIs, and Fexuprazan has the potential to lead the transition". Aside from the poster presentations at DDW 2023, Daewoong successfully held a special event outside of the traditional DDW session, "Fexuclue Reception Night" held in Chicago, USA on May 8th (local time). At Fexuclue Reception Night, about 70 key opinion leaders from around the world, including executives from Korean and overseas digestive societies, actively discussed the features of P-CAB including Fexuprazan as well as the treatment guideline for GERD using P-CAB. Lee Chang-jae, CEO of Daewoong Pharmaceutical said, "We had the opportunity to showcase the potential effectiveness of Fexuprazan to doctors and researchers specializing in gastrointestinal diseases at the world's largest conference, DDW 2023 during the presentation of study results related to the erosive reflux disease that can be treated by Fexuprazan", adding "We have plans and ongoing clinical trials in and out of the country, aiming to expand the range of diseases that can be treated by Fexuprazan. We will concentrate our resources on gathering data that can demonstrate the efficacy of Fexuprazan and developing various formulations to enhance the value of Fexuprazan." About Fexuprazan Fexuprazan is investigational new drug in the United States of America. Outside the United States of America, Fexuprazan is known with a brand name of Fexuclue for GERD treatment. Fexuclue is an approved prescription drug for the treatment of GERD in South Korea, Chile, Ecuador and the Philippines. Fexuclue is registered trademarks of Daewoong Pharmaceutical. Any other trademarks referred to in this press release are the property of their respective owners. Forward-Looking Statements This press release contains forward-looking statements that are based on the current beliefs and expectations of Daewoong Pharmaceutical's management. These statements are subject to various risks, uncertainties, and assumptions that could cause actual results to differ materially from those anticipated in such forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to: (1) Regulatory and governmental approvals: The approval process for pharmaceutical products is subject to extensive regulations and may involve uncertainties and delays. Any failure to obtain necessary approvals or the occurrence of delays in the approval process could adversely affect Daewoong Pharmaceutical's business and results of operations; and (2) Clinical trials: The success of Daewoong Pharmaceutical's products depends on the results of clinical trials. The results of early clinical trials may not be indicative of the results of later-stage or larger-scale clinical trials. Company Codes: Korea:069620

ProSense System among the two types of systems used in the study Pain-free survival rates of 93.75% at 6 months and 82.72% at 36 months post-procedure 190 million women globally live with endometriosis, for which there is no cure; current treatments aim to control symptoms Data presented at Society of Interventional Radiology 2023 Annual Scientific Meeting by lead investigator Francois H. Cornelis, MD, PhD CAESAREA, Israel, April 20, 2023 /PRNewswire/ -- IceCure Medical Ltd. (Nasdaq: ICCM) (TASE: ICCM) developer of minimally-invasive cryoablation technology, the ProSense® System, that destroys tumors by freezing as an alternative to surgical tumor removal, today announced that its ProSense system was used in a single-site study conducted at the Sorbonne University Department of Interventional Radiology and Oncology, Tenon Hospital in Paris, France by lead investigator Francois H. Cornelis, MD, PhD and a team of doctors. The study titled "Pain-Free Survival After Percutaneous Image-Guided Cryoablation of Extraperitoneal Endometriosis" was published in the Journal of Vascular and Interventional Radiology. The independent study and published paper were not sponsored by IceCure. Dr. Cornelis presented the study data at the Society of Interventional Radiology 2023 Annual Scientific Meeting on March 8, 2023. Cryoprobes used in the study were of two types: IceCure's ProSense cryoprobe and Varian's V-probe. The purpose of the study was to retrospectively evaluate the pain-free survival of percutaneous (minimally invasive, through the skin) image-guided cryoablation of symptomatic extraperitoneal endometriosis ("EE"). 42 patients with a total of 47 lesions were treated. Patients were made aware that cryoablation was offered as a minimally invasive alternative to surgery, and that a surgical procedure may be performed if cryoablation failed. According to the published study, the therapeutic options thus far to avoid the progression of endometriosis and reduce symptoms have been limited to hormonal agents and wide surgical excision. During the last decades, minimally invasive techniques such as cryoablation have been suggested as a promising option to treat abdominal wall endometriosis with satisfactory outcomes and low morbidity. Based on the following study outcome data, the study concluded that percutaneous cryoablation is a safe and effective procedure that significantly reduces pain and obtains local control of EE. The median follow-up was 13.5 months after cryoablation. The study's conclusions included: Efficacy rate of cryoablation to avoid secondary surgery was 92.8% per patient and 93.6% per nodule treated Median pain-free survival rates were 93.75% at 6 months and 82.72% after 12 months, 24 months, and 36 months Pain decreased from a median of 8/10 on the visual analogue scale to 0/10 at the last follow-up (P < 0.0001) 4 patients had an adverse event in the days following the procedure, 1 patient had a severe adverse event. "We are grateful to Dr. Cornelis and the team of doctors at Sorbonne University and Tenon Hospital, where the data was collected, for having used our ProSense system, in addition to those from another company, as part of this independent study. Tenon Hospital institution is highly regarded in the field of gynecology and interventional radiology. We believe that the independent study has demonstrated the value of cryoablation in treating endometriosis, a chronic and painful condition in dire need of an effective minimally invasive treatment," stated Eyal Shamir, IceCure's Chief Executive Officer. "The ProSense system has regulatory approval in several countries, including FDA clearance for use as a cryosurgical tool in gynecology, and we are pleased that doctors now have more evidence of cryoablation's efficacy in patients with extraperitoneal endometriosis." According to the World Health Organization, endometriosis affects about 10% of women who are at reproductive age globally, or 190 million people. Endometriosis is a chronic disease associated with severe, life-impacting symptoms. Many individuals suffering from it have limited awareness of the condition causing a lengthy delay between onset of symptoms and diagnosis. Current treatments are aimed at controlling symptoms. EE may be observed incidentally but more often on surgical scars in women with or without a history of endometriosis. About IceCure Medical IceCure Medical (Nasdaq: ICCM) (TASE: ICCM) develops and markets ProSense®, an advanced liquid-nitrogen-based cryoablation therapy for the treatment of tumors (benign and cancerous) by freezing, with the primary focus areas being breast, kidney, bone and lung cancer. Its minimally invasive technology is a safe and effective alternative to hospital surgical tumor removal that is easily performed in a relatively short procedure. The system is marketed and sold worldwide for the indications cleared and approved to date including in the U.S., Europe, and China. Logo - IR Contact: Michael Polyviou Email: [email protected] 732.232.6914 Todd Kehrli Email: [email protected] SOURCE IceCure Medical